Over the past 2 weeks, the U.S. Food and Drug Administration (FDA) granted Priority Review to a treatment for acute myeloid leukemia (AML); Fast Track designations for agents in pancreatic cancer and pancreatic/nonpancreatic neuroendocrine tumors; approvals for companion diagnostic tests; Breakthrough Therapy designation for an investigational agent in some lung cancers; Orphan Drug designation to a new treatment for AML; and regenerative medicine advanced therapy to a CAR T-cell therapy for follicular lymphoma.
Priority Review for Oral Azacitidine for the Maintenance Treatment of Patients With AML in Remission
The FDA accepted a new drug application for oral azacitidine, an investigational oral hypomethylating agent, for the maintenance treatment of adult patients with acute myeloid leukemia (AML) who achieved complete remission or complete remission with incomplete blood count recovery following induction therapy with or without consolidation treatment and who are not candidates for, or who choose not to proceed to, hematopoietic stem cell transplantation. The FDA granted the application Priority Review and set a Prescription Drug User Fee Act goal date of September 3, 2020.
The new drug application submission was based on the efficacy and safety results of the phase III QUAZAR AML-001 study, which met its primary endpoint of improved overall survival for patients receiving AML maintenance treatment with oral azacitidine vs placebo. Key secondary endpoints included relapse-free survival, safety and tolerability, and health-care resource utilization and patient-reported outcomes per the FACIT-Fatigue Scale and EQ-5D questionnaire.
The study enrolled 472 patients, who were randomly assigned 1:1 to receive initially either 300 mg of oral azacitidine or placebo once daily for 14 days of a 28-day cycle plus best supportive care. Patients remained on treatment until unacceptable toxicity or disease progression.
Fast Track Designation for Eryaspase as Second-Line Treatment for Pancreatic Cancer
The FDA granted Fast Track designation to eryaspase as a second-line treatment of patients with metastatic pancreatic cancer.
Eryaspase is a novel treatment comprising L-asparaginase encapsulated inside a donor-derived red blood cell, aimed at targeting cancer cells’ altered amino acid metabolism. It is being evaluated in a phase III trial, TRYbeCA-1, which is taking place in 11 countries in Europe and the United States.
More than 75% of the approximately 500 patients enrolled in the trial have been assigned to a treatment arm. Eligible patients are randomly assigned 1:1 to receive eryaspase in combination with standard chemotherapy (gemcitabine/nab-paclitaxel or an irinotecan-based regimen) or chemotherapy alone.
The primary endpoint of TRYbeCA-1 is overall survival. An interim superiority analysis will be conducted when approximately two-thirds of the events have occurred.
In a previous phase IIb trial, eryaspase demonstrated significant improvement in both overall survival and progression-free survival, with a hazard ratio of 0.60 and 0.59, respectively. Overall, eryaspase was well tolerated and showed a safety profile comparable to that of standard chemotherapy.
Fast Track Designations for Surufatinib for the Treatment of Both Pancreatic and Nonpancreatic Neuroendocrine Tumors
The FDA granted two Fast Track designations for the development of surufatinib—for the treatment of both advanced and progressive pancreatic neuroendocrine tumors and extrapancreatic (nonpancreatic) neuroendocrine tumors in patients who are not amenable to surgery.
Surufatinib is a novel oral angio-immuno kinase inhibitor that selectively inhibits the tyrosine kinase activity associated with vascular endothelial growth factor receptor and fibroblast growth factor receptor, which both inhibit angiogenesis, and colony stimulating factor 1 receptor, which regulates tumor-associated macrophages, promoting the body’s immune response against tumor cells. Its unique dual mechanism of action may be very suitable for possible combinations with other immunotherapies.
There is an ongoing multicohort phase Ib study studying surufatinib in solid tumors.
Approval for PD-L1 Companion Diagnostic on Dako Omnis to Identify Patients With Lung Cancer to Receive First-Line Immunotherapy
The FDA approved the PD-L1 IHC 22C3 pharmDx assay as a companion diagnostic to identify patients with non–small cell lung cancer who are appropriate for first-line monotherapy with pembrolizumab on the Dako Omnis platform.
Dako Omnis is a fully automated, walk-away solution for staining tumor samples that provides a flexible, high-throughput diagnostic service integrated into the core of the laboratory workflow.
FDA approval for cobas HPV Test for Use on cobas 6800/8800 Systems to Identify Women at Risk for Cervical Cancer
The FDA approved the cobas HPV test for use on the fully automated, high-throughput cobas 6800/8800 systems. The cobas HPV test identifies women at risk for cervical cancer by detecting the presence of high-risk human papillomavirus (HPV) DNA in cervical samples.
The cobas HPV test is indicated for use for routine cervical cancer screening as per professional medical guidelines, including triage of ASC-US cytology, cotesting (or adjunctive screen) with cytology, and HPV primary screening of women to assess the risk for cervical precancer and cancer.
The FDA considered data from the registrational IMPACT (IMproving Primary screening And Colposcopy Triage) trial, which enrolled almost 35,000 women in the United States to clinically validate cobas HPV for use on the cobas 6800/8800 Systems. Study data will be broadly shared, pending publication of the key findings.
Breakthrough Therapy Designation for Mobocertinib for Patients With NSCLC and EGFR Exon 20 Insertion Mutations
The FDA granted Breakthrough Therapy designation for the investigational drug mobocertinib for the treatment of patients with metastatic non–small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy. There are currently no approved therapies designed to treat this specific form of NSCLC. Mobocertinib is a small-molecule tyrosine kinase inhibitor designed to selectively target EGFR and HER2 exon 20 insertion mutations.
The Breakthrough Therapy designation is based on the overall response rate and the long-term benefit seen in patients who responded to the therapy in a phase I/II study evaluating the safety and efficacy of mobocertinib in patients with locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion mutations and have been previously treated with systemic chemotherapy. Data on the agent was shared this week at the American Association for Cancer Research Virtual Annual Meeting (Abstract DDT02-03).
Results from the ongoing phase I/II trial of mobocertinib, which is evaluating the efficacy and safety of mobocertinib at 160 mg once daily in previously treated patients with NSCLC and EGFR exon 20 insertions, showed mobocertinib yielded a median progression-free survival of 7.3 months and a confirmed overall response rate of 43% in patients with locally advanced or metastatic EGFR exon 20 insertion–mutant NSCLC. The safety profile of mobocertinib was manageable; the most common treatment-related adverse events were diarrhea (in 85% of patients), nausea (43%), rash (36%), vomiting (29%) and decreased appetite (25%). These results were presented at the 2019 ASCO Annual Meeting (Abstract 9007).
Orphan Drug Designation for MT-401 for Acute Myeloid Leukemia
The FDA granted Orphan Drug designation to MT-401, a multitumor-associated antigen-specific T-cell product for the treatment of patients with acute myeloid leukemia following allogeneic stem cell transplant.
The manufacturer commented that the candidate was “well-tolerated” and produced “clinical benefit across various liquid and solid tumors, suggesting the product candidate's ability to induce a patient's own T cells to expand for a more durable antitumor effect.”
Regenerative Medicine Advanced Therapy Designation for Tisagenlecleucel in Follicular Lymphoma
The FDA granted Regenerative Medicine Advanced Therapy (RMAT) designation to tisagenlecleucel for an investigational new indication to treat patients with relapsed or refractory follicular lymphoma. Tisagenlecleucel, which is designed to be a one-time treatment, is the first-ever FDA-approved chimeric antigen receptor T-cell therapy.
The RMAT designation program is part of the 21st Century Cures Act. The program was created to expedite the development and review of regenerative medicine therapies intended to treat, modify, reverse, or cure a serious condition. The FDA granted RMAT designation for tisagenlecleucel in follicular lymphoma based on preliminary clinical evidence from the ELARA clinical trial, an ongoing multicenter, phase II study to determine the efficacy and safety of tisagenlecleucel in adult patients with relapsed or refractory follicular lymphoma.
